The most common clinico-pathologic manifestation of exposure to environmental neurotoxins is degeneration of long and large nerve fibers (axons). Most research on these diseases during the past decade has addressed the degenerating nerve fiber; little interest has focused on the nerve cell body (soma), despite its established role in maintaining and repairing the axon. My initial studies in intoxicated rats have shown a spectrum of morphologic changes, suggesting an orchestrated pattern of cell body remodeling. The current five year proposal is directed towards understanding how cell body remodeling and cell body-axon interactions act to determine the fate of intoxicated neurons. Secondarily, it will help provide the scientific basis for screening pollutants for neurotoxicity, and provide information about the basic biology of chromatolysis. Experimental rats will be intoxicated with the prototype neurotoxins 2,5-hexanedione and acrylamide monomer to study axons and cell bodies using quantitated light and electron microscopy, autoradiography, and histofluorescence techniques. A first set of experiments will study motoneurons and dorsal root ganglion neurons in relation to axonal degeneration. It will address the specificity and early evolution of cell body remodeling and correlate this with autoradiographic data on RNA and protein metabolism. A second set of experiments will study cell body and axon changes in identified portions of the sympathetic (autonomic) nervous system. Investigation will focus on questions of specific vulnerability and the pattern of cell body-axon changes; morphologic changes will be correlated with metabolic data on RNA and protein synthesis, and with histofluorescent investigation of neurotransmitter in cell body and axon.